Monitoring the Swedish population-level neutralisation of current and emerging SARS-CoV-2 variants (SwedN)
PI(s)/Head responsible for the resource:
Ben Murrell
Host organisation(s):
Karolinska Institutet
Resource description:
From an overwhelming array of evidence from clinical trials, observational studies, and animal models, the most reliable correlate of protection from SARS-CoV-2 infection, and from severe disease, is neutralising antibody potency. With potent neutralising antibodies against a circulating SARS-CoV-2 variant, the individual is less likely to be infected and less likely to develop severe disease if infected.
While large amounts of money are spent on virus sequencing to monitor circulating SARS-CoV-2 variants, it is difficult to convert this “variant prevalence” information into an assessment of risk without knowing the distribution of antibody responses against these circulating variants. As our recent widely-publicised results have shown, this can be exceptionally population specific: substantial cross-neutralisation of Omicron BA.1, for example, was far more common in a random cohort of Swedish blood donors, and even more so in infected-then-vaccinated Swedish hospital workers, than it was in twice-vaccinated cohorts from other countries. The population-specific “exposure history”, including the extent of vaccination and the distribution of infection rates with various variants, strongly influences the breadth and potency of antibody responses.
Thus, there is an unacknowledged public health gap: SARS-CoV-2 neutralisation surveillance. If we know how susceptible the population is, on average, to the set of variants that is likely to emerge (or in the process of emerging) in the next wave, we can make data-driven population-specific recommendations about additional booster vaccinations and additional precautions, and whether they are likely to be needed or not.
Here we propose to use our already well-established SARS-CoV-2 pseudovirus (PSV) neutralisation platform to address this gap, providing ongoing near-real-time monitoring of population-level antibody potency against a spectrum of SARS-CoV-2 variants in local populations.
Research findings:
At various points, this project provided some of the earliest data characterizing the degree of escape of emerging variants. For example. approaching the winter of 2022, we published two rapid communications on variants that exemplified the “convergently evolving” set of variants, with very similar mutational profiles, that came to dominate the winter season. These exhibited substantial, but not complete, escape from neutralizing antibodies in contemporaneous local blood donor samples, and escaped all-but-one clinically-approved monoclonal antibodies (escaping all that were approved in Europe). Additionally, when BA.2.86 emerged, with a degree of genetic divergence that rivalled the original Omicron emergence, we rapidly demonstrated that this variant did not exhibit an exceptional escape profile. These results were communicated to policy organizations, cited in recommendations, and reported in the popular press. Additionally, this project contributed to the development of a SARS-CoV-2 global model of variant competition, which incorporates global SARS-CoV-2 sequencing data and estimates which variants are currently growing the fastest across all countries reporting data. This has aided in prioritizing variants to functionally screen for this PLP2 project. The model is publicly available on GitHub and has been incorporated into the Pathogens Portal as a dashboard. The outputs of this model have been tracked by various stakeholders and policy organizations (including the ECDC) and have served as the basis for collaborations with a lab in the US (published in Nature) as well as a lab in Australia (resulting in multiple publications).
Additionally, neutralization assays from this project supported a variety of research collaborations on SARS-CoV-2 immunology and antibody responses. These included animal studies of immunization strategies, studies of vaccine responses in the elderly in Sweden, and detailed studies of specific antibodies to understand, for example, how the ability to neutralize multiple variants of SARS-CoV-2 arises.
Impact on prepardness for future pandemics:
The primary societal benefits of this project and its outcomes were the near-real-time results about the degree to which emerging variants escape from antibodies. Data such as this can have public health impact, informing decisions about the need for adapted vaccines, the expected efficacy of monoclonal antibody therapies, and the potential need (or lack thereof) for further non-pharmaceutical interventions and restrictions. There was also a substantial direct public interest in the results, as evidenced by the press attention and online social media discussion.
Contact information:
Ben Murrell
Assistant Professor
Email: benjamin.murrell@ki.se